Growth Factors, Their Receptor Expression and Markers for Proliferation of Endothelial and Neoplastic Cells in Human Osteosarcoma

E. Bianchi, M. Artico, C. Di Cristofano, M. Leopizzi, S. Taurone, M. Pucci, P. Gobbi, F. Mignini, V. Petrozza, I. Pindinello, M.T. Conconi, C. Della Rocca
2013 International Journal of Immunopathology and Pharmacology  
Although avoidance of occupational triggers remains the primary step in the management of workrelated allergies, immunological treatments (including biological agents and specific immunotherapy) can be regarded as potential therapeutic options for IgE-mediated diseases; for example, many studies with allergen-specific immunotherapy have been carried out on latex allergy, showing overall favorable results, at least with sublingual immunotherapy. On the other hand, only few case reports have
more » ... sted the efficacy of immunotherapy in baker's asthma as well as in laboratory animal-induced asthma. The new technologies, including component-resolved diagnosis and recombinant allergens, are expected to improve the quality and efficacy of specific immunotherapy in the future. Also the use of omalizumab may represent a suitable therapeutic choice in very selected cases of occupational allergy, as well as an approach to reduce side effects of venom immunotherapy in subjects with previous severe reactions to the treatment. Systemic lupus erythematosus (SLE) is the prototype of autoimmune diseases with multiorgan involvement. SLE presents many genetic and epigenetic associations and the pathogenesis is characterized by a complex network of alterations affecting both adaptative and innate immunity. The disclosure of novel mechanisms of SLE pathogenesis suggested new therapeutic targets, based on interference with the cytokine pathways or on depletion of the immune cells. Mast cells are inflammatory cells, and they are prominent in inflammatory diseases such as allergy and asthma. Mast cells possess high-affinity receptors for IgE (FcεRI) and the cross-linking of these receptors is essential to trigger the secretion of granules containing arachidonic acid metabolism [such as prostaglandin (PG) D2, leukotriene (LT) B4, and LTC4], histamine, cytokines, chemokines, and proteases, including mast cell-specific chymases and tryptases. Activation of mast cells provokes the secretion of cytokines and mediators that are responsible for the pathologic reaction of immediate hypersensitivity. Sensory nerve stimulation by irritants and other inflammatory mediators provokes the release of neuropeptides, causing an increase in vascular permeability, plasma extravasation and edema. Trigeminal nerve stimulation actives dura mast cells and increases vascular permeability, effects inhibited by capsaicin. Capsaicin causes release of sensory neuropeptide, catecholamines and vasodilation. Several studies have reported that capsaicin is effective in relief and prevention of migraine headaches, improves digestion, helps to prevent heart disease, and lowers blood cholesterol and blood pressure levels. The findings reported in these studies may have implications for the pathophysiology and possible therapy of neuroinflammatory disorders. Hypoxia-inducible factor-1α (HIF-1α) has been reported to have an important role in the metabolism and synthesis of extracellular matrix of the nucleus pulposus cells (NPCs) and was assumed to be involved in the process of intervertebral disc degeneration. The objective of this study was to investigate the role of HIF-1α in disc degeneration in vivo using a conditional HIF-1α knockout (KO) mouse model. ShhCre transgenic mice were mated with HIF-1α fl/fl mice to generate conditional HIF-1α KO mice (HIF-1α fl/fl -ShhCre + ). Three mice of each genotype (Wide-type and HIF-1α KO) at the age of 3 days, 6, and 12 weeks were sacrificed after genotyping. Five lumbar disc samples were harvested from each mouse, with a total of 45 disc samples for each genotype. In situ hybridization and immunohistochemical analysis were used to check the efficacy of HIF-1α knockout. Histological grading of the disc degeneration was performed according to the classification system proposed by Boos et al. Picro-sirius red staining, Safranine O/ fast green staining and immunohistochemical study were used to evaluate the expression of aggrecan, type-II collagen and vascular endothelial growth factor (VEGF). Histologic analysis revealed more NPC deaths and signs of degeneration in HIF-1α KO mice and the degeneration scores of HIF1-α KO mice were significantly higher than those of the Wide-type mice at the age of 6 weeks and 12 weeks. There were less expressions of aggrecan, type-II collagen and VEGF in the intervertebral discs of HIF1-α KO mice than in those of wild-type mice. Taken together, the results of our study indicated that HIF-1α is a pivotal contributor to NPC survival and the homeotasis of extracellular matrix through the HIF-1α/ VEGF signaling pathway, and plays an important role in the development of disc degeneration. Osteosarcoma is the most common primary malignant tumour of the bone. Although new therapies continue to be reported, osteosarcoma-related morbidity and mortality remain high. Modern medicine has greatly increased knowledge of the physiopathology of this neoplasm. Novel targets for drug development may be identified through an understanding of the normal molecular processes that are deeply modified in pathological conditions. The aim of the present study is to investigate, by immunohistochemistry, the localisation of different growth factors and of the proliferative marker Ki-67 in order to determine whether these factors are involved in the transformation of osteogenic cells and in the development of human osteosarcoma. We observed a general positivity for NGF -TrKA -NT3 -TrKC -VEGF in the cytoplasm of neoplastic cells and a strong expression for NT4 in the nuclear compartment. TGF-β was strongly expressed in the extracellular matrix and vascular endothelium. BDNF and TrKB showed a strong immunolabeling in the extracellular matrix. Ki-67/MIB-1 was moderately expressed in the nucleus of neoplastic cells. We believe that these growth factors may be considered potential therapeutic targets in the treatment of osteosarcoma, although proof of this hypothesis requires further investigation. Pneumonia is an inflammation of the lung caused by microbial or viral infection. It is an important factor of morbidity for children in the developed world, as well as a frequent cause of death of children in the developing world. Chemokines are a very important part of the immune system. The purpose of this study was to investigate the role of polymorphisms of chemokine RANTES (-28C/G and-403G/A) in the development of pneumonia in children. The study included two groups of children, the patient group and the control group. The patient group consisted of 60 children, who were hospitalized with the diagnosis of pneumonia from November 2009 until May 2010. The control group consisted of 135 healthy children who had no previous history of lower respiratory tract infections. According to the results, polymorphism of chemokine RANTES -28C/G was associated to the development of pneumonia in the studied population. Polymorphism of chemokine RANTES -403G/A was not associated to the development of pneumonia in the same population. Serum levels of chemokine RANTES were lower in children who were carriers of the polymorphism -28C/G compared to children who had the normal gene type. Also, serum levels of chemokine RANTES were higher in children with pneumococcal pneumonia compared to children with pneumonia caused by other pathogens. Prosthetic rehabilitation improves the patient's quality of life and oral health. The purpose of the present study was to assess the production of volatile sulfur compounds (VSCs) using Oral Chroma™ in patients wearing provisional and permanent fixed prosthesis, who were treated or not, with supportive non-surgical periodontal therapy. A total of 10 healthy patients not affected by periodontal disease and who needed the restoration of at least two edentulous single sites were included in the present study. Registrations of VSCs were carried out with a Gas Chromatograph OralChroma™ (Oral Chroma™, Abimedical, Abilit Corp., Osaka, Japan) one month after placement of the provisional restoration (group 1) and one month after placement of the final restoration (group 3). After each measurement, professional oral hygiene was carried out both on patients with provisional (group 2) and permanent prostheses (group 4) and VSC values were registered. The results showed that there were no statistical significant differences in the VSC quantity between groups with temporary or permanent prostheses. Meanwhile, statistically significant differences were found in VCS values between groups before and after the professional health care session (p < 0.05). Also it was observed that dimethyl sulphide (CH 3 ) 2 S was present in all the study groups. The present preliminary study suggests that OralChroma™ produce a comprehensive assessment of VSC in the clinical diagnosis of halitosis and that professional oral hygiene seems to influence VSC production. However, further clinical long-term studies with a larger sample size are necessary for a better understanding of halitosis manifestation in patients wearing provisional and permanent fixed prosthesis. The aim of this experimental study was to evaluate the effects of nicotine on sperm motility and on nonconventional sperm parameters in vitro. Capacitated spermatozoa isolated from 10 normozoospermic, healthy, non-smoker men were evaluated. Spermatozoa were exposed to increasing concentrations of nicotine (0, 1, 10, and 100 ng/ml) for 3 and 24 hours. Progressive motility and the following nonconventional sperm parameters, evaluated by flow cytometry, were assessed: mitochondrial membrane potential, viability, phosphatidylserine externalization, late apoptosis, degree of chromatin compactness, and DNA fragmentation. Nicotine suppressed, in a concentration-dependent manner, sperm progressive motility starting from the lowest concentration used (1 ng/ml). Similarly, it reduced the percentage of viable spermatozoa and increased the number of spermatozoa in late apoptosis, with altered chromatin compactness, or DNA fragmentation already after 3 hours of incubation. These effects were observed at a concentration similar (100 ng/ml) to that found in the seminal plasma of smokers (70 ng/ml), with the exception of the effects on sperm DNA fragmentation whose significant effect was detected also at a lower concentration (10 ng/ml). Nicotine may be regarded as a noxious component of cigarette smoke on the male reproductive function. Specific human leukocyte antigen (HLA) DQB1 alleles confer strong susceptibility to systemic sclerosis (SSc). However, the frequencies of specific DQB1 alleles and their associations with SSc vary according to ethnicity and clinical features of SSc. The aim of this study was to profile DQB1 alleles in a Chinese population and to identify specific DQB1 alleles in association with SSc of Han Chinese. A cohort containing 213 patients with SSc and 239 gender-matched and unrelated controls was examined in the study. The HLA-DQB1 genotyping was performed with sequence-based typing (SBT) method. Exact p-values were obtained (Fisher's test) from 2x2 tables of allele counts or allele carriers and disease status. Seventeen DQB1 alleles were found in the cohort. DQB1*03:03 was the most common allele in this cohort. DQB1*05:01 was significantly increased in SSc, and was strongly associated with anticentromere autoantibodies (ACA). Compared with SSc in other ethnic populations, SSc patients of Han Chinese are distinct in association with DQB1 The active role of chemokines and inflammatory cytokines in the central nervous system (CNS) during the pathogenesis of experimental autoimmune encephalomyelitis (EAE) has been clearly established. Recent studies from our laboratory reported that Huperzine A (HupA) can attenuate the disease process in EAE by the inhibition of inflammation, demyelination, and axonal injury in the spinal cord as well as encephalomyelitic T-cell proliferation. In this study, the effects of low dose HupA on CCL2, TNF-α, IL-6, and IL-1β expression were evaluated in EAE. The effect of HupA on lipopolysachharide (LPS)-induced inflammatory molecule secretion was investigated in cultured-astrocytes in vitro. In MOG 35-55 -induced EAE mice, intraperitoneal injections of HupA (0.1 mg/kg·d −1 ) significantly suppressed the expression of CCL2, IL-6, TNF-alpha, and IL-1beta in the spinal cord. HupA also repressed LPS-induced CCL2 production, but with little influence on pro-inflammatory cytokines in primary cultured astrocytes. The inhibition effect of HupA on CCL2 is PPARγ-dependent and nicotine receptor-independent. Conditioned culture media from HupA-treated astrocyte decreased PBMC migration in vitro. Collectively, these results suggest that HupA can ameliorate EAE by inhibiting CCL2 production in astrocyte, which may consequently decrease inflammatory cell infiltration in the spinal cord. HupA may have a potential therapeutic value for the treatment of MS and other neuroinflammatory diseases. The hypercoagulability of patients with nephrotic syndrome could be an important trigger for arterial and venous thrombotic events. Arterial thromboses are less frequent than venous thromboses and the most common locations are femoral arteries. The association of stroke and nephrotic syndrome is extremely rare. Here we report the case of a patient with stroke as first manifestation of nephrotic syndrome. Ischemic stroke can be the first manifestation of nephrotic syndrome and should be considered as a possible complication of the syndrome, when the commonest causes of ischemic stroke are excluded and especially in presence of pre-existing glomerular disease. The treatment choice for metastatic breast cancer should consider the appropriate balance between efficacy and toxicity of the therapy. We discuss a clinical case with an early response and prolonged to liposomal anthracyclines-based chemotherapy, without cardiotoxicity, enhancing the evidence of safety of liposomal formulation to prevent heart damage. Moreover, the case seems to be of interest for the role of 18 F-FDG-PET in clinical response assessment: an early decrease of the standardized uptake value value, even before conventional imaging evaluation, is highly predictive for prolonged clinical response. Fifteen Klebsiella pneumoniae clinical isolates showing non-susceptibility to carbapenems and resistant to colistin were collected in an Italian hospital. All isolates resulted negative to AmpC, MBL and ESBL production but positive to modified Hodge test, therefore were evaluated as KPC producers. The presence of blaKPC genes was verified by polymerase chain reaction (PCR) and sequencing. Furthermore, molecular typing was performed by multilocus sequence typing (MLST). PCR analysis and nucleotide sequencing revealed that all 15 isolates carried the blaKPC-3 gene. MLST analysis attributed the isolates from all patients to belong to the sequence type ST512. All isolates showed extensively drug-resistant (XDR) phenotype. The emergence of colistin-resistant K. pneumoniae underscores the implementation of strict control measures to prevent the dissemination of these organisms in hospitals. We describe the case of a child affected by milk-protein induced enterocolitis, in which oral challenge with corn was performed without symptoms after a negative specific Atopy Patch Test. Food protein-induced enterocolitis syndrome (FPIES) is an uncommon non-IgE-mediated gastrointestinal food hypersensitivity of infancy, characterized by severe vomiting and diarrhea arising within 1 to 3 hours after ingestion of the causative food. Little is known about the pathophysiology of FPIES. The absence of food-specific IgE as demonstrated by negative skin prick tests suggests that the disease is not caused by an early onset IgEmediated reaction. Atopy Patch Test has been described as sensitive and predictive in this syndrome. The hypothesis on the immunological pathogenesis has been discussed on the basis of literature data. Osteoarthritis (OA) is a chronic degenerative joint disorder characterized by destruction of the articular cartilage, subchondral bone alterations and synovitis. Matrix metalloproteinases (MMPs) are expressed in joint tissues of patients with osteoarthritis (OA). The objective of this study was to define the steady state levels of two different MMPs to provide more insight into the role of MMPs in cartilage destruction in OA. We investigated the expression of gelatinases through immunohistochemistry Our results show that high levels of MMP-2 and MMP-9 are present in OA and suggest that once these MMPs are fully activated they may contribute to the cartilage destruction in OA. Psoriatic arthritis is a chronic, inflammatory, disabling arthritis affecting up to 30% of psoriatic patients. Recently, it has been demonstrated that tumor necrosis factor alpha (TNF-α) plays a pivotal role in inducing and maintaining joint damage and that molecules that block this cytokine are effective in the treatment of psoriatic arthritis. Etanercept is a recombinant fusion protein acting as a competitive inhibitor of TNF-α, and numerous clinical trials have demonstrated its efficacy in determining psoriatic arthritis remission. However, specific criteria defining psoriatic arthritis remission have not been delineated and few data describing the length of the remission after etanercept discontinuation are available. The aim of this observational, retrospective study was to assess post-remission efficacy maintenance and relapse characteristics after etanercept interruption in patients with moderate-tosevere peripheral psoriatic arthritis (PsA) and cutaneous involvement.
doi:10.1177/039463201302600306 pmid:24067459 fatcat:izp6dkiorja6bdtt5nrzvkwhg4